Development of a genetically integrated PBPK model for predicting uric acid homeostasis in humans
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Publication Details
Author list: Kaewlin N., Liangruksa M., Laomettachit T.
Publication year: 2021
Journal: Thai Journal of Mathematics (1686-0209)
Volume number: 19
Issue number: 3
Start page: 854
End page: 864
Number of pages: 11
ISSN: 1686-0209
Languages: English-Great Britain (EN-GB)
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Abstract
Serum uric acid (SUA) balance is mainly regulated by the excretion and reabsorption by the kidneys. Much attention has recently been focused on the genetic variation of renal uric acid transporter genes that affect uric acid homeostasis. Here, we have developed a system of equations to study the human uric acid homeostasis using the physiologically based pharmacokinetic (PBPK) model. The PBPK model incorporates blood flow and tissue compartment of organs to describe how uric acid is distributed within the body. We have also implemented the concept of sub-compartments within the kidneys that allows the model to integrate the genetics of individual patients. We chose to model patients with single nucleotide polymorphisms (SNPs) on the SLC2A9 gene (encoding the urate transporter protein, GLUT9) because the gene variation directly affects the amount of uric acid excreted and reabsorbed by the kidneys. SUA levels predicted from our model simulations of the wild-type and several variants of GLUT9 show good agreement with the experimental observations. Our model development results in a framework for implementing genetic factors as a subsystem of PBPK modeling while giving way to a better representation of human physiology in a highly complex system. © 2021 by TJM.
Keywords
Physiologically based pharmacokinetic modeling, Uric acid homeostasis
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